In a normal human heart, the sinus node, generally located near the junction of the superior vena cava and the right atrium, constitutes the primary natural pacemaker initiating rhythmic electrical excitation of the heart chambers. The cardiac impulse arising from the sinus node is transmitted to the two atrial chambers, causing a depolarization known as a P-wave and the resulting atrial chamber contractions. The excitation pulse is further transmitted to and through the ventricles via the atrioventricular (A-V) node and a ventricular conduction system causing a depolarization known as an R-wave and the resulting ventricular chamber contractions.
Disruption of this natural pacing and conduction system as a result of aging or disease can be successfully treated by artificial cardiac pacing using implantable cardiac stimulation devices, including pacemakers and implantable defibrillators, which deliver rhythmic electrical pulses or other anti-arrhythmia therapies to the heart, via electrodes implanted in contact with the heart tissue, at a desired energy and rate. One or more heart chambers may be electrically stimulated depending on the location and severity of the conduction disorder.
A single-chamber pacemaker delivers pacing pulses to one chamber of the heart, either one atrium or one ventricle. Dual chamber pacemakers are now commonly available and can provide stimulation in both an atrial chamber and a ventricular chamber, typically the right atrium and the right ventricle. Both unipolar or bipolar dual chamber pacemakers exist in which a unipolar or bipolar lead extends from an atrial channel of the dual chamber device to the desired atrium (e.g., the right atrium), and a separate unipolar or bipolar lead extends from a ventricular channel to the corresponding ventricle (e.g., the right ventricle). In dual chamber, demand-type pacemakers commonly referred to as DDD pacemakers, each atrial and ventricular channel includes a sense amplifier to detect cardiac activity in the respective chamber and an output circuit for delivering stimulation pulses to the respective chamber.
If an intrinsic atrial depolarization signal (a P-wave) is not detected by the atrial channel, a stimulating pulse will be delivered to depolarize the atrium and cause contraction. Following either a detected P-wave or an atrial stimulation pulse, the ventricular channel attempts to detect a depolarization signal in the ventricle, known as an R-wave. If no R-wave is detected within a defined interval, a stimulation pulse is delivered to the ventricle to cause ventricular contraction. In this way, rhythmic dual chamber pacing is achieved by coordinating the delivery of ventricular output in response to a sensed or paced atrial event.
The interval following an atrial stimulation pulse prior to delivery of a ventricular stimulation pulse is commonly referred to as an “AV delay.” The interval following an atrial sensed P-wave prior to delivering a ventricular stimulation pulse is commonly referred to as a “PV delay.” The AV delay is typically programmed to be longer than a PV delay because an atrial stimulation pulse is delivered at a location away from the direct conduction path of an intrinsic depolarization arising from the sinus node and traveling to the ventricles.
It is known that the AV and PV delay settings during dual chamber pacing can have profound effects on hemodynamic function, particularly in patients suffering from heart failure. Extreme differences in cardiac output can result from different AV and PV delay settings. Mounting clinical evidence supports the use of dual chamber or multi-chamber stimulation in patients suffering from congestive heart failure even if normal conduction pathways are intact. In these patients, the therapeutic benefit of cardiac stimulation is thought to be derived from a resynchronization of the heart chamber contractions. The dilatation of the heart that occurs with the progression of heart failure impairs the normal synchrony of heart chamber contractions. Therefore, careful selection of the AV and PV delays in these patients can provide hemodynamic benefit.
Methods used by physicians to monitor the progression of heart failure or a response to heart failure therapy include echocardiographic techniques for measuring heart dimensions and estimating ejection fraction, catheterization techniques for measuring blood pressures and volumes, and exercise testing. These monitoring methods can only be performed periodically in a clinical setting and can be costly as well as pose additional risk to the patient.
Numerous attempts have been made, therefore, to develop an implantable cardiac stimulation device that includes one or more physiological sensors for measuring cardiac function. Proposed methods have suggested using pressure sensors, flow transducers, impedance measurement for estimating chamber volumes, accelerometers for detecting heart motion, temperature sensors, pH sensors, and oxygen sensors for monitoring heart function. The difficulty in incorporating such sensors in an implantable cardiac stimulation device is the added hardware and complex circuitry needed to support and process sensor data. For example, both the blood ejection phase of the cardiac cycle, known as “systole”, and the filling phase of the cardiac cycle, known as “diastole”, can be impaired in congestive heart failure. In fact, congestive heart failure symptoms may be attributed to diastolic dysfunction in a significant number of congestive heart failure patients. Diastolic dysfunction is particularly common in elderly patients.
Clinically, diastolic dysfunction is difficult to detect and assess without performing echocardiography. Diastolic dysfunction may be present when systolic function is adequate and symptoms of congestive heart failure are absent. Treatments for diastolic dysfunction therefore remain relatively under-investigated. Monitoring of diastolic function over time, using a method that does not require expensive or invasive methods that can be performed in a clinic would be advantageous in diagnosing diastolic dysfunction and optimizing its treatment.
The cardiac signal produced in response to a stimulation pulse that depolarizes the heart has been found to be proportional to ventricular chamber volume. When a stimulation pulse is delivered to a ventricle, an evoked response electrocardiogram signal is produced. The integral of the negative portion of the evoked response signal, referred to hereafter as the “paced depolarization integral,” has been found to be inversely proportional to end-diastolic volume. The paced depolarization integral has already been proposed as a measure of cardiac volume upon which adjustments in AV delay can be based in an effort to maximize the heart's ejected blood volume during cardiac stimulation.
It would be desirable, however, to also provide a diagnostic method for monitoring changes in heart function over time using an implantable cardiac stimulation device without requiring additional physiological or metabolic sensors. In particular, it would be desirable to monitor diastolic function over time using the paced depolarization integral so that worsening or improving diastolic function can be tracked and therapy delivery could be adjusted accordingly. Preferably, this is accomplished using standard sensing of internal cardiac electrogram (EGM) signals without complex software requirements and without requiring physician office visits.